1. Field of the Invention
The present invention relates generally to the treatment of brain disorders, and more particularly, to a hybrid neuroprosthesis apparatus implanted subcutaneously in a human subject.
2. Prior Art
At the dawn of the year 2000, effective therapy is still unavailable for the treatment of Alzheimer""s disease and other degenerative disorders, stroke is still the third leading cause of death in the United States after heart disease and cancer, and currently marketed drugs are still ineffective in about 60% of patients with complex partial seizures. These few examples may demonstrate that the challenges for neurology and psychiatry in the new century will be as enormous as the achievements of these medical fields in the past one. New therapeutic strategies are needed, which capitalize on the progress in drug research, molecular biology, computer technology and electronics. Constructing neuroprosthetic devices is part of these efforts.
The first generation of successful neuroprosthesis included diaphragm pacing devices to stimulate the phrenic nerve in patients with respiratory paralysis, the Neurocybernetic Prosthesis for seizure control via vagus nerve stimulation, and cochlear implants for acoustic nerve stimulation in individuals with hearing loss. A second generation of neuroprostheses, designed to restore sensory and motor functions are under development in various laboratories. A common feature of these existing and experimental neuroprosthetic devices is that they stimulate the neural tissue electrically.
However, the neurons of the brain are not merely living electronic machines. While these cells indeed transmit information to other neurons with the use of purely electrical tools referred to as xe2x80x9caction potentialsxe2x80x9d, the generation and spacing of action potentials are regulated by molecular mechanisms. In fact, these mechanisms are sophisticated interplays of a large number of intra- and extracellular molecular systems. Thus, the neurons work as molecular-electronic computers, as they process their inputs with molecular mechanisms in order to generate electrical outputs.
The hybrid neuroprosthesis device of the present invention is essentially the translation of the dual: molecular-electronic nature of neurons into a medical device. The term xe2x80x9chybrid neuroprosthesisxe2x80x9d refers to a subcutaneously implanted miniature apparatus which simultaneously acts as an electrophysiological data recorder and a drug delivery means such as a pump. This allow it to monitor the electrical activity of a dysfunctioning brain area and to correct the dysfunction by delivering drugs into the environment of the abnormal neurons.
Accordingly, the hybrid neuroprosthesis of the present invention fundamentally differs from all prior neuroprostheses, as the hybrid neuroprosthesis aims to correct neural dysfunctions pharmacologically, and not electrically. The advantage of the hybrid neuroprosthesis approach is that with drugs neuron- and synapse-specific actions can be achieved, which is difficult to accomplish with electrical stimulations.
The hybrid neuroprosthesis of the present invention also differs from the intracerebral drug delivery technologies of the prior art. No prior intracerebral drug delivery systems, including drug-loaded ethylene vinyl acetate copolymer (EVAc) rods, are able to monitor the electrical activity of the targeted brain tissue. As a consequence, no feed-back is obtained from the targeted tissue. This may lead to too high, therefore damaging, or too low, therefore ineffective, drug concentrations. No prior intracerebral drug delivery systems can apply the drug solutions periodically, only when this intervention is necessary.
Indeed, a device is needed which is able to monitor the electrical activity of a dysfunctioning brain area without interfering with the patient""s daily life, yet also being able to deliver drugs into the dysfunctioning brain area: precisely when it is necessary. The hybrid neuroprosthesis device of the present invention satisfies this need, especially since the device can also be extended to monitoring not only the electrical but also the neurochemical activity of the dysfunctioning brain area and to deliver drugs into this area in response to either the neurochemical signals, or the electrical signals, or both.
Therefore, it is an object of the present invention to provide apparatus and methods for the treatment of brain disorders which overcomes the problems of the prior art.
It is a further object of the present invention to provide apparatus and methods for the treatment of brain disorders which stimulates brain tissue by pharmacological stimulation.
It is yet a further object of the present invention to provide apparatus and methods for the treatment of brain disorders which can be used in controlled human studies.
It is yet a further object of the present invention to provide apparatus and methods for the treatment of brain disorders for analyzing neuronal firing in natural circumstances, during behavior.
It is yet a further object of the present invention to provide apparatus and methods for the treatment of brain disorders in which a delivered drug solution does not affect the cells of the whole body which can drastically change the subject""s behavior.
It is still yet a further object of the present invention to provide apparatus and methods for the treatment of brain disorders which regulates intracerebral drug delivery.
Accordingly, an apparatus for the treatment of brain disorders in a subject is provided. The apparatus comprises: a drug delivery means implanted in the subject for delivering at least one drug solution to the brain of the subject; a drug driving means that drives the at least one drug solution to the drug delivery means; a recording electrode implanted in the brain for outputting an electrical signal characteristic of an electrical activity of the brain; and a microcontroller for controlling the drug driving means on the basis of the electrical signal. Preferably, the entire apparatus is subcutaneously disposed in the subject. Preferably, the recording electrode is complemented with a sensor to detect neurochemical signals such as neurotransmitter release or other molecular events. Alternatively, the recording electrode is replaced by a neurochemical sensor.
The drug delivery means is preferably a cannula, such as a multi-port cannula having a plurality of ports, each port delivering the drug solution to a corresponding portion of the brain or an intraventricular cannula for delivering the drug solution to a substantial portion of the brain. Alternatively, the drug delivery means can be a catheter, microdialysis probe, or other drug ejector device. The drug delivery means is implanted in the brain of the subject or in the ventricular system of the subject.
The drug driving means is preferably a pump, that includes a drug reservoir for holding the at least one drug solution and which is also preferably subcutaneously disposed in the subject and is externally accessible on the surface of the skin for periodic refilling. Alternatively, the drug driving device can be a microcapillary device, nanotube, microtube, microfabricated pathway using electrokinetic force, or other components.
The apparatus preferably further comprises an electrical signal conditioner disposed between the recording electrode and the microcontroller for amplifying, filtering and digitizing the recorded electrical signals from the brain and inputting the conditioned signals to the microcontroller, wherein the electrical signal conditioner is also preferably subcutaneously disposed in the subject.
The microcontroller is preferably equipped with a microprocessor, to analyze the electrophysiological data stream from the electrical signal conditioner and regulate the drug driving means accordingly. Alternatively, the microcontroller can be a digital signal processor (DSP), a programmable logical array (PLA), a programmable logical device (PLD), an application-specific integrated circuit (ASIC), or other similar device. The processor can be equipped with a transmitter to transmit, preferably via a communication system, the analyzed electrophysiological signals to outside of the body for more advanced human and computer analysis. The processor is preferably further equipped with a receiver to receive, preferably via a communication system, human and computer commands from outside of the body.
The apparatus still further comprises a power source, such as a battery, for supplying power to the drug driving device, the microcontroller and the electrical signal conditioner. The battery is preferably a NiMH or Lithium-ion battery which is also subcutaneously disposed in the subject and is rechargeable from the outside of the body from an electromagnetic or optical power source. Alternatively, the power source is a subcutaneous current generator.
In a preferred configuration of the apparatus, the microcontroller, the drug driving means, the electrical signal conditioner and the battery are housed in a single container subcutaneously disposed in the subject. The container is preferably an elastomer case fabricated from medical grade silicon and is subcutaneously disposed in the subject at the base of the brain and back of the neck. Alternatively, the microcontroller, the drug driving means, the electrical signal conditioner and the power source can be housed in individual containers, located in distant body parts under the skin, and are interconnected via subcutaneous tunneling.
Also provided are methods for the treatment of brain disorders with the apparatus of the present invention.